Fast Dissolving Tablets Using Natural Superdisintegrating Agents: A Review

The oral route is the most widely used route of drug administration because it is convenient, non-invasive, economical and well accepted by patients. However, swallowing a conventional tablet or capsule is difficult for many people, including children, the elderly, bedridden patients, patients with nausea or persistent vomiting, and those who have no ready access to water. Difficulty in swallowing (dysphagia) often leads to missed doses and poor therapeutic outcomes.[1,2,3]

Fast dissolving tablets (FDTs), also called orally disintegrating or mouth dissolving tablets, are placed on the tongue, where they disintegrate or dissolve in the saliva within seconds, without water and with little or no chewing; the resulting dispersion is then swallowed. The US FDA guidance describes an orally disintegrating tablet as one that disintegrates rapidly in the mouth, with a disintegration time of about 30 seconds or less.[4] An ideal FDT needs no water, disintegrates within seconds, leaves little or no residue, has a pleasant taste and mouthfeel, is strong enough to withstand handling and can be made by a simple and economical method.[1,3,5]

The performance of an FDT depends mainly on the superdisintegrant. Synthetic superdisintegrants such as croscarmellose sodium, crospovidone and sodium starch glycolate are effective, but plant mucilages and gums are cheap, biodegradable, generally safe and easily available, and they have been studied as natural superdisintegrants and binders.[6,7,8]

Advantages and Limitations

Table: Advantages and Limitations of Fast Dissolving Tablets[1,3,5]

Technologies for Fast Dissolving Tablets

Several technologies are used to prepare FDTs, and they differ in cost, tablet strength and the equipment needed.[1,2,3] Freeze drying gives very fast dissolution but is costly and the product is fragile.[9] Direct compression is the simplest and most economical method.[3]

Table: Technologies Used for Fast Dissolving Tablets[2,3,9]

Superdisintegrants

A superdisintegrant acts by one or more mechanisms: swelling (particles absorb water and enlarge, breaking the tablet structure), wicking or capillary action (water is drawn rapidly into the tablet through pores) and deformation recovery (particles deformed during compression return to their shape when wetted).[5,10,11]

Figure 1: Mechanisms of Action of Superdisintegrants

Table: Comparison of Synthetic Superdisintegrants and Natural Mucilages[5,6,12]

Natural Mucilages as Superdisintegrants

Plant mucilages are hydrophilic polysaccharides, which hydrate and swell rapidly in water. Mucilages from the seeds or husk of Isapgol (Plantago ovata), Linseed (Linum usitatissimum), Aliv or garden cress (Lepidium sativum) and Fenugreek (Trigonella foenum-graecum) have been reported as disintegrants and binders in tablets, and all four plants are easily available in Maharashtra.[7,8,13,14,15,16,17]

Table: Natural Sources of Mucilage Used in Fast Dissolving Tablets[6,7,8]

Method of Isolation of Mucilage

The mucilage is generally isolated by extraction with water followed by precipitation with a non-solvent.[7,8,17] The steps are described below.

Step 1: Collection and Cleaning

The seeds or husk are purchased from a reliable source, authenticated and cleaned to remove foreign matter.

Step 2: Soaking and Heating

About 10 g of the material is soaked in 200 mL of distilled water for 12 to 24 hours and then heated gently on a water bath for about 30 minutes, so that the mucilage is released into the water.

Step 3: Separation of the Mucilage

The mass is squeezed through muslin cloth to separate the seeds or husk from the mucilage.

Step 4: Precipitation

The filtered mucilage is precipitated by adding about twice its volume of ethanol (or acetone), and the precipitate is separated and washed.

Step 5: Drying, Powdering and Storage

The precipitate is dried in a hot air oven at 45 to 50 °C, powdered, passed through sieve no. 80 and stored in a desiccator.

Figure 2: Isolation of Mucilage from Seeds or Husk

Characterisation of the Mucilage

Table: Tests for Characterisation of Isolated Mucilage[6,8,17]

Method of Preparation of Fast Dissolving Tablets by Direct Compression

Direct compression is the simplest and most economical method, as it uses ordinary tablet-making equipment and needs no heat or solvent.[3,10] It also allows the effect of the superdisintegrant to be studied without interference from other process variables.

Step 1: Weighing and Sieving

The drug, superdisintegrant, diluents (mannitol, microcrystalline cellulose) and sweetener are weighed accurately and passed through sieve no. 60.

Step 2: Blending

The ingredients are blended thoroughly in a polybag or a blender, so that the drug and the disintegrant are distributed uniformly.

Step 3: Addition of Lubricant and Glidant

Magnesium stearate and talc are added last and mixed for 3 to 5 minutes, since longer mixing of the lubricant can weaken the tablet and slow its disintegration.[11]

Step 4: Compression

The blend is compressed on a single-punch or rotary tablet machine to the target weight, keeping the hardness the same in all batches, so that differences in disintegration can be attributed to the type and level of the disintegrant.

Figure 3: Direct Compression Method for Fast Dissolving Tablets

Table: Typical Composition of a Fast Dissolving Tablet[5,10,12]

Selection of the Drug

A drug for an FDT should be of low dose, stable, and have an acceptable taste or one that can be masked. Anti-emetic drugs such as ondansetron are often chosen as model drugs, since patients with nausea and vomiting cannot easily swallow tablets with water and need a rapid onset.[1,2]

Evaluation of Fast Dissolving Tablets

The blend is evaluated before compression and the tablets after compression. The tests, methods and expected results are given below.[4,5,10]

Table: Evaluation of Fast Dissolving Tablets[4,5,10,11]

Review of Literature

Seager (1998) described the development of the Zydis fast-dissolving dosage form, one of the first commercial fast-dissolving products, which is prepared by freeze drying and dissolves almost instantly in the mouth.[9] Habib et al. (2000) reviewed fast-dissolve drug delivery systems and the technologies used to make them, their advantages and their limitations, such as taste, mechanical strength and moisture sensitivity.[1]

Fu et al. (2004) reviewed orally fast disintegrating tablets, covering the manufacturing technologies, taste masking and clinical studies, and pointed out that the choice of disintegrant strongly influences the disintegration time and mouthfeel.[2] Bandari et al. (2008) gave an overview of orodispersible tablets and highlighted direct compression as the simplest and most economical method, and Bhowmik et al. (2009) discussed the mechanisms of superdisintegrants and the quality-control tests.[3,5] The US FDA guidance (2008) describes the characteristics expected of an orally disintegrating tablet, including a disintegration time of about 30 seconds or less.[4]

Kulkarni et al. (2002) evaluated the binding property of mucilages of Plantago ovata and Trigonella foenum-graecum in tablets, and Kumar et al. (2009) isolated mucilage from fenugreek seeds and evaluated its disintegrant properties.[7,8] Shirsand et al. (2009) used Plantago ovata mucilage as a superdisintegrant in fast disintegrating tablets of prochlorperazine maleate, and reported that the batch with 8% mucilage dispersed in about 8 seconds and released the drug faster than the conventional tablet.[13]

Shrotriya et al. (2010) studied the disintegration properties of Linum usitatissimum mucilage in dispersible tablets of diltiazem hydrochloride, and reported that it was more efficient than starch.[14] Inamdar et al. (2012) described the isolation and evaluation of fenugreek and flaxseed mucilages as pharmaceutical binders.[17] Goyal et al. (2013) developed fast dissolving tablets of losartan potassium using mucilages of Plantago ovata and Lepidium sativum, and Prajapati et al. (2014) made fast-dissolving tablets of aceclofenac with natural superdisintegrants, including Lepidium sativum seed mucilage.[15,16]

Table: Summary of Studies on Natural Mucilages in Tablets[7,8,13,14,15,16,17]

Research gap

Most studies examined one mucilage at a time, in different model drugs, at different concentrations and by different methods, so the natural agents cannot be compared directly. Few studies compare several seed mucilages with a synthetic superdisintegrant in the same formulation and under the same conditions.[13,14,15,16]

CONCLUSION

Fast dissolving tablets help patients who cannot swallow conventional tablets, and direct compression is a simple and economical way of making them. The superdisintegrant decides the disintegration time, and natural mucilages of Isapgol, Linseed, Aliv and Fenugreek are cheap, biodegradable, locally available alternatives to synthetic superdisintegrants, which have been reported to give rapid disintegration and quick drug release.

However, natural mucilages vary with their source and method of extraction, and are mostly non-official, so they need proper characterisation and quality control. Further work is required to compare the mucilages in the same formulation with a synthetic control, to study taste masking, toxicity and stability, and to confirm the performance in more model drugs and in vivo.

REFERENCES

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2. Fu Y, Yang S, Jeong SH, Kimura S, Park K. Orally fast disintegrating tablets: developments, technologies, taste-masking and clinical studies. Crit Rev Ther Drug Carrier Syst. 2004;21 (6):433-476.
3. Bandari S, Mittapalli RK, Gannu R, Rao YM. Orodispersible tablets: an overview. Asian J Pharm. 2008;2 (1):2-11.
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7. Kulkarni GT, Gowthamarajan K, Rao BG, Suresh B. Evaluation of binding property of Plantago ovata and Trigonella foenum-graecum mucilage. Indian Drugs. 2002;39:422-425.
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13. Shirsand SB, Suresh S, Para MS, Swamy PV, Nagendra Kumar D. Plantago ovata mucilage in the design of fast disintegrating tablets. Indian J Pharm Sci. 2009;71 (1):41-45.
14. Shrotriya S, Patwardhan SK, Pandit AP, Khandelwal AP, More KS, Jain KS. Study of disintegration properties of mucilage from Linum usitatissimum in the formulation of dispersible tablet. Indian Drugs. 2010;47 (8):35-42.
15. Prajapati ST, Patel MV, Patel CN. Formulation and evaluation of fast-dissolving tablets of aceclofenac using natural superdisintegrants. Int J Pharm Sci Res. 2014;5:483-487.
16. Goyal R, Nagpal M, Arora S, Dhingra GA. Development and optimization of fast dissolving tablets of losartan potassium using natural gum mucilage. J Pharm Technol Res Manag. 2013.
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